Acquired resistance of B16 tumor cells to protons after prolonged fractional electron irradiation

Cancer radiotherapy effectiveness largely depends on tumor cells radiosensitivity. Inherent or acquired radioresistance of tumor cells is important challenge in radiation therapy. Response of tumor cells to fractionated radiation therapy has been investigated by many research groups. At present time the use of protons for cancer research and treatment has expanded rapidly. In this connection research on sensitivity of tumor cells to proton beam therapy is an urgent task. The aim of the study was to assess sensitivity of irradiated with electrons or protons B16 melanoma cells to the next electron beam or proton beam irradiation at comparable total doses. Studies with the use of stable tumor cell lines with acquired radioresistance may be useful for the development of effective treatment plan tailored to the patients with relapses or metastases that have occurred after prior unsuccessful radiotherapy with standard types of radiation. Protons were provided by Prometeus installation scanning beam and the electron beam of the accelerator Novac-11. Cells radiosensitivity was measured by clonogenic assay. The resistance of cells first irradiated with protons and electrons to the next irradiation with protons and electrons was estimated by clonogenic assay. DNA damages, cell size, proliferative activity and cell cycle phase distribution were also evaluated. The study demonstrated that fractionated irradiation of B16 cells with electrons at the total dose of 60 Gy causes significant reduction of cells radiosensitivity to the next irradiation with protons, radiosensitivity of irradiated cells to the second irradiation with electrons remains the same. In contrast, the first fractionated irradiation of cells with protons at the total dose of 50 Gy does not affect the radiosensitivity of the cells to the next irradiation with electrons or protons.